Clinical phenotype and genetic analysis of RPS19, RPL5, and RPL11 genes in Greek patients with Diamond Blackfan Anemia

Delaporta, Polyxeni; Sofocleous, Christalena; Stiakaki, Eftichia; Polychronopoulou, Sophia; Economou, Marina; Kossiva, Lydia; Kostaridou, Stavroula; Kattamis, Antonis

doi:10.1002/pbc.25183

Cited by 13 publications

(10 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1,8,37 Congenital malformations were seen in 55.8% of patients, which is significantly lower than the incidence in a Greek group of patients (71%), yet higher than the incidence of congenital defects in a large cohort of Chinese patients (19.7%). 43,44 In comparison with previously reported large patient cohorts including the North American Registry (DBAR), a comparable incidence of congenital malformations (47% vs 55.8%) was observed.…”

Section: Discussionsupporting

confidence: 54%

Pediatric Diamond‐Blackfan anemia in the Netherlands: An overview of clinical characteristics and underlying molecular defects

Dooijeweert

Ommen

Smiers

et al. 2017

European J of Haematology

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 54%

Pediatric Diamond‐Blackfan anemia in the Netherlands: An overview of clinical characteristics and underlying molecular defects

Dooijeweert

Ommen

Smiers

et al. 2017

European J of Haematology

View full text Add to dashboard Cite

show abstract

“…For example, our registry and the Italian registry 33 show similar number of RPL5 and RPL11 patients (~10% of each group), while other registries found a much smaller proportion of RPL11 patients. 14,34,35 Increased awareness to the unique phenotype of RPL11 genetic group as suggested by the results of our study will facilitate earlier diagnosis, enable counseling about the cancer risk associated with DBA, 7 as well as counseling and testing of other family members.…”

Section: Discussionmentioning

confidence: 80%

Molecular analysis and genotype‐phenotype correlation of Diamond‐Blackfan anemia

et al. 2017

View full text Add to dashboard Cite

Diamond-Blackfan anemia (DBA) features hypoplastic anemia and congenital malformations, largely caused by mutations in various ribosomal proteins. The aim of this study was to characterize the spectrum of genetic lesions causing DBA and identify genotypes that correlate with phenotypes of clinical significance. Seventy-four patients with DBA from across Canada were included. Nucleotide-level mutations or large deletions were identified in 10 ribosomal genes in 45 cases. The RPS19 mutation group was associated with higher requirement for chronic treatment for anemia than other DBA groups. Patients with RPS19 mutations, however, were more likely to maintain long-term corticosteroid response without requirement for further chronic transfusions. Conversely, patients with RPL11 mutations were less likely to need chronic treatment. Birth defects, including cardiac, skeletal, hand, cleft lip or palate and genitourinary malformations, also varied among the various genetic groups. Patients with RPS19 mutations had the fewest number of defects, while patients with RPL5 had the greatest number of birth defects. This is the first study to show differences between DBA genetic groups with regards to treatment. Previously unreported differences in the rate and types of birth defects were also identified. These data allow better patient counseling, a more personalized monitoring plan, and may also suggest differential functions of DBA genes on ribosome and extra-ribosomal functions.

show abstract

“…The DBA database (Boria et al., , ) included 129 RPS19 mutations in 219 patients at its last update in 2010. We reviewed the literature to collect additional RPS19 mutations identified more recently and now have a total of 165 different RPS19 mutations reported in 313 DBA patients (Arbiv et al., ; Chae et al., ; Da Costa et al., ; Delaporta et al., ; Errichiello et al., ; Farrar et al., ; Gerrard et al., ; Ichimura et al., ; Konno et al., ; Kuramitsu et al., ; Landowski et al., ; Ozono et al., ; Pospisilova et al., ; Quarello et al., ; Smetanina et al., ; Solomon et al., ; Tsangaris et al., ; van Dooijeweert et al., ; Wang et al., ; Zhang et al., ). For our study, we selected only those variants for which there was no strong evidence of pathogenicity according to the genetic criteria outlined in Materials and Methods, and obtained 47 VUS reported in 122 patients (39% of RPS19‐mutated patients, approximately 10% of all DBA patients).…”

Section: Resultsmentioning

confidence: 99%

A functional assay for the clinical annotation of genetic variants of uncertain significance in Diamond-Blackfan anemia

et al. 2018

View full text Add to dashboard Cite

Diamond–Blackfan anemia (DBA) is a rare genetic hypoplasia of erythroid progenitors characterized by mild to severe anemia and associated with congenital malformations. Clinical manifestations in DBA patients are quite variable and genetic testing has become a critical factor in establishing a diagnosis of DBA. The majority of DBA cases are due to heterozygous loss‐of‐function mutations in ribosomal protein (RP) genes. Causative mutations are fairly straightforward to identify in the case of large deletions and frameshift and nonsense mutations found early in a protein coding sequence, but diagnosis becomes more challenging in the case of missense mutations and small in‐frame indels. Our group recently characterized the phenotype of lymphoblastoid cell lines established from DBA patients with pathogenic lesions in RPS19 and observed that defective pre‐rRNA processing, a hallmark of the disease, was rescued by lentiviral vectors expressing wild‐type RPS19. Here, we use this complementation assay to determine whether RPS19 variants of unknown significance are capable of rescuing pre‐rRNA processing defects in these lymphoblastoid cells as a means of assessing the effects of these sequence changes on the function of the RPS19 protein. This approach will be useful in differentiating pathogenic mutations from benign polymorphisms in identifying causative genes in DBA patients.

show abstract

Clinical phenotype and genetic analysis of RPS19, RPL5, and RPL11 genes in Greek patients with Diamond Blackfan Anemia

Abstract: The clinical course of the patients was similar to previous reports. The occurrence of thyroid carcinoma in an adult patient with DBA is the first to be reported in DBA.

Cited by 13 publications

References 36 publications

Pediatric Diamond‐Blackfan anemia in the Netherlands: An overview of clinical characteristics and underlying molecular defects

Pediatric Diamond‐Blackfan anemia in the Netherlands: An overview of clinical characteristics and underlying molecular defects

Molecular analysis and genotype‐phenotype correlation of Diamond‐Blackfan anemia

A functional assay for the clinical annotation of genetic variants of uncertain significance in Diamond-Blackfan anemia

Contact Info

Product

Resources

About